FETO With Long Tail Balloon for a Treatment of Severe CDH (LongTailFETO)

The Intrauterine Fetoscopic Tracheal Occlusion (FETO) With Long Tail Balloon for a Treatment of Severe Congenital Diaphragmatic Hernia (CDH)

Congenital diaphragmatic hernia (CDH) has an incidence of 1:2200 to 1:4000 newborns. The survival rate depends on the extent of the lung hypoplasia and pulmonary hypertension. In case of an observed / expected total fetal lung volume ratio (o/e TFLV) ratio of 25% or lower and herniation of the liver in thorax, the postnatal survival is estimated to be 10-25% or lower. The aim of fetoscopic tracheal balloon occlusion is to positively influence the lung growth in CDH fetuses avoiding the development of lung hypoplasia.

Some complications after sucsessfull FETO before delivery occur because of technical difficulties during the extraction of the balloon from the trachea, leading to asphyxia, worse outcome or neonatal demise. Jani et al. published 10 neonatal deaths from 210 FETO directly related to difficulties with the removal of the intratracheal balloon. The risk of emergent balloon removal was published to be very high (39%-56%).

Our new technique exploits the fetal ability to removal the intratracheal balloon which has been implanted for the treatment of severe CDH before the delivery, avoiding many risks associated with balloon extraction and a second fetoscopy.

The study will be performed on 20 fetuses with severe CDH. Before the FETO the total fetal lung volume ratio (o/e TFLV) will be measured by fetal MRI (magnetic . Only CDH fetuses with 24-32 weeks' gestation with o/e TFLV < 25% or the fetuses with o/e TFLV < 35% and liver herniation will be operated Second fetal MRI should be performed in one week after the FETO. The balloon will be extracted by the fetus itself before the delivery, after puncture with 22 gauge needle under ultrasound guiding, during second fetoscopy or using the EXIT (ex utero intrapartum Treatment). Neonatal follow up 12 months.

Study Overview

• Status: Unknown
• Conditions: Severe Congenital Diaphragmatic Hernia
• Intervention / Treatment: Device: Long Tail Balloon

Detailed Description

Congenital diaphragmatic hernia (CDH) has an incidence of 1:2200 to 1:4000 newborns, depending on whether stillbirths are included or not. 40 % of all CDH cases show associated malformations and chromosomal abnormalities and/or syndromes take place in 10-20%. The survival rate depends on the extent of the lung hypoplasia and pulmonary hypertension. Liver herniation into the thorax, is also a negative predictor of fetal survival. In case of an observed / expected total fetal lung volume ratio (o/e TFLV) ratio of 25% or lower and herniation of the liver in thorax, the postnatal survival is estimated to be 10-25% or lower. The aim of fetoscopic tracheal balloon occlusion is to positively influence the lung growth in CDH fetuses avoiding the development of lung hypoplasia.

A common complication of fetal surgery is the preterm premature rupture of membranes (PPROM) leading to preterm delivery. The next problem occurs because of technical difficulties during the extraction of the balloon from the trachea, leading to asphyxia, worse outcome or neonatal demise. Jani et al. published 10 neonatal deaths from 210 FETO directly related to difficulties with the removal of the intratracheal balloon. The risk of emergent balloon removal was published to be very high (39%-56%).

Our new long tail balloon exploits the fetal ability to removal the intratracheal balloon which has been implanted for the treatment of severe CDH before the delivery, avoiding many risks associated with balloon extraction and a second fetoscopy.

The study will be performed on 20 fetuses with severe CDH with total fetal lung volume ratio (o/e TFLV) < 25% or with o/e TFLV < 35% combined with liver herniation into the thorax. The lung volume will be estimated by fetal MRI. The selected fetuses with severe CDH at 24-32 weeks' gestation will be operated.

Before the Long tail FETO the 0.1 mg/kg Pancuronium, 1 µg/kg Fentanyl® and 0.01 mg/kg atropine will be applicated i.m. to the CDH fetus using 22 gauge needle under ultrasound control. The monofilament 5-0 polypropylene suture of 7 cm will be fixed to the balloon (Goldbal 5, 2,5 ml, BALT Extrusion, Montmorency, France) and the FETO will be performed. The fetoscope (Karl Storz, Tuttlingen, Germany) with a diameter of 1.3 mm will be percutaneously inserted through a sheath into the uterus and then into the fetal trachea. The fetoscope will be removed and the long tail balloon will be inserted under 4-D ultrasound guidance.The position of the balloon and suture will be controlled by fetoscopy and sonography.

Second fetal MRI should be performed in one week after the FETO. The balloon must be extracted before the delivery.

Possibilities of the Long tail extraction:

1. The fetus is able to extract the balloon from the trachea after FETO, by pulling the balloons' long tail, at the end of pregnancy;
2. by fetus itself after balloon puncture with 22 gauge needle under ultrasound guiding;
3. during second fetoscopy;
4. or using the EXIT procedure.

The CDH will be closed with / or without a patch. The follow up examinations will be performed at 6 and 12 months of age the baby.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Michael Tchirikov, MD, PhD; Phone Number: +49-345-557-3250; Email: michael.tchirikov@uk-halle.de
• Study Contact Backup: Name: Michael Bergner, MD; Email: michael.bergner@uk-halle.de

Study Locations

• Germany
  • Halle, Germany, 06120
    • Recruiting
    • Center of Fetal Surgery, Clinic of Obstetrics and Perinatal Medicine, Martin-Luther-University Halle-Wittenberg
    • Contact: Michael Tchirikov, MD, PhD; Phone Number: 0493455573250; Email: geburtshilfe@uk-halle.de
    • Contact: Kathrin Reinsdorf; Phone Number: 0493455573245; Email: reinsdorf@uk-halle.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 46 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• maternal age of 18-48 years
• severe CDH with MRI measured observed/expected total fetal lung volume (o/e TFLV) < 25% or < 35% in combination with a liver herniation into the thorax.

Exclusion Criteria:

• fetuses with other letal morphological abnormalities
• fetuses with chromosomal abnormalities
• severe maternal illneses

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Long-Tail-FETO; Fetus with severe CDH and o/e TFLV Ratio of < 25% or < 35% with liver herniation. The Long tail FETO will performed between 26 and 30 weeks of gestation. The MRI control will be perfirmed ar 32-34 weeks of gestation. Long Tail FETO: fetal i.m. application of 0.1 mg/kg Pancuronium, 1 µg/kg Fentanyl® and 0.01 mg/kg atropine. ("Long-Tail" Goldbal 5, 2,5 ml, BALT Extrusion, Montmorency, France). The fetoscope (Karl Storz, Tuttlingen, Germany) with a diameter of 1.3 mm, will be percutaneously inserted through a sheath into the uterus and then into the fetal trachea. The fetoscope will be removed and the balloon will be inserted under 4-D ultrasound guidance into the fetal trachea. The position of the balloon and suture will be visualized using the fetoscopy. The Long tail ballon will be removed by a second FETO after 34 weeks' gestation or bei the fetus itself with or without of the long tail balloon puncture with 22 gauge needle. The EXIT procedure is also possible.

Device: Long Tail Balloon; s. description of experimental Arm

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
neonatal survival	survival rate	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pulmonary hypoplasia	clinical presence of pulmonary hypoplasia (yes - Grade /no)	1 year
Diaphragmatic Hernia operation	Patch (yes/no)	1 year
necrotizing enterocolitis	yes / no	1 year
neurodevelopmental impairment	(yes, - Grade /no)	1 year
APGAR	APGAR (1st/5th/10th min)	during the first 10 min after the delivery
umbilical artery pH	pH measument in the umbilical artery	during 10 min after the delivery
weight	weight in (g)	24hour
length	neonatal length in cm	24hour
Duration of O2-Ventilation (day)	Duration of O2-Ventilation (day)	1 year

Collaborators and Investigators

• Sponsor: Martin-Luther-Universität Halle-Wittenberg
• Investigators: Principal Investigator: Michael Tchirikov, MD, PhD, Germany, Center of Fetal Surgery, Martin-Luther University Halle-Wittenberg

Publications and helpful links

General Publications

• Jani JC, Nicolaides KH, Gratacos E, Valencia CM, Done E, Martinez JM, Gucciardo L, Cruz R, Deprest JA. Severe diaphragmatic hernia treated by fetal endoscopic tracheal occlusion. Ultrasound Obstet Gynecol. 2009 Sep;34(3):304-10. doi: 10.1002/uog.6450.
• Tchirikov M, Gatopoulos G, Strohner M, Puhl A, Steetskamp J. Two new approaches in intrauterine tracheal occlusion using an ultrathin fetoscope. Laryngoscope. 2010 Feb;120(2):394-8. doi: 10.1002/lary.20687.
• Tchirikov M. Successful tracheal occlusion using ultrathin fetoscopic equipment combined with real-time three-dimensional ultrasound. Eur Surg Res. 2009;43(2):204-7. doi: 10.1159/000224146. Epub 2009 Jun 10.

Study record dates

Study Major Dates

• Study Start (Actual): August 30, 2017
• Primary Completion (Anticipated): August 30, 2020
• Study Completion (Anticipated): August 30, 2021

Study Registration Dates

• First Submitted: January 24, 2018
• First Submitted That Met QC Criteria: February 12, 2018
• First Posted (Actual): February 13, 2018

Study Record Updates

• Last Update Posted (Actual): February 13, 2018
• Last Update Submitted That Met QC Criteria: February 12, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Keywords: CDH, FETO, fetal surgery, long tail FETO
• Additional Relevant MeSH Terms: Congenital Abnormalities; Pathological Conditions, Anatomical; Internal Hernia; Hernia; Hernias, Diaphragmatic, Congenital; Hernia, Diaphragmatic
• Other Study ID Numbers: 2017-104

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes

IPD Plan Description

All patients:

only the Nr. of the patient will be available, diagnosis, diaphragmatic hernia left or right, liver herniation, o/e total volume lung ration (%), gestational age at the Operation (long tail FETO), gestational age of the delivery, PPROM (yes/no), APGAR, art. pH, weight.

• IPD Sharing Time Frame: when summary data are published
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR); Analytic Code

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No